Involvement of somatic stem cells in encapsulation of foreign–body reaction in canine subcutaneous Biotube tissue formation

Abstract

Generally, the thickness of tubular tissues formed from silicone rods through encapsulation of the foreign-body reaction is less than approximately 0.2mm. On the other hand, it is unclear how hollow cylindrical molds can provide thick tubular tissues, known as Biotubes, with a thickness exceeding 1mm, during in-body tissue architecture (iBTA) using encapsulation. In this study, histological and structural analyses were performed to understand the reason for the formation of thick mold-based Biotubes. Molds were assembled with a gap between a silicone rod and a stainless-steel cylinder and were embedded into the dorsal subcutaneous pouches of beagles for 2 or 4 weeks. Thick Biotubes were obtained from the harvested mold. The histological analysis showed that the lumen side of the thick Biotubes consisted primarily of type I collagen fibers and α-smooth muscle actin-positive cells, similar to the original rod-based thin Biotubes formed only from silicone rods. Interestingly, the outer region of the thick Biotubes was an immature connective tissue consisting of type III collagen, including primitive somatic stem cells expressing CD90 and SSEA4. These stem cells may have contributed to the formation of the thick-walled Biotubes by differentiating into other cell types and through growth factor production. Because of the potential tissue-repair ability of these stem cells, iBTA could be useful for elucidating the regeneration process, remodeling the physiology/pathology of tissue defects/damage, and cell acquisition. This technology can provide autologous stem cells without invitro cell culture. Moreover, thick-walled Biotubes may be useful as an alternative stem cell-containing material in regenerative medicine.